Statin Use for the Primary Prevention of Cardiovascular Disease in Adults
Authors: Roger Chou, Amy Cantor, Tracy Dana, Jesse Wagner, Azrah Y. Ahmed, Rongwei Fu, Maros Ferencik
Journal: JAMA (2022)

<h3>Importance</h3> A 2016 review for the US Preventive Services Task Force (USPSTF) found use of statins for primary prevention of cardiovascular disease (CVD) was associated with reduced mortality and cardiovascular outcomes. <h3>Objective</h3> To update the 2016 review on statins for primary prevention of CVD to inform the USPSTF <h3>Data Sources</h3> Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (to November 2021); surveillance through May 20, 2022. <h3>Study Selection</h3> Randomized clinical trials on statins vs placebo or no statin and statin intensity in adults without prior cardiovascular events; large cohort studies on harms. <h3>Data Extraction and Synthesis</h3> One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. <h3>Main Outcomes and Measures</h3> All-cause and cardiovascular mortality, myocardial infarction, stroke, composite cardiovascular outcomes, and adverse events. <h3>Results</h3> Twenty-six studies were included: 22 trials (N = 90 624) with 6 months to 6 years of follow-up compared statins vs placebo or no statin, 1 trial (n = 5144) compared statin intensities, and 3 observational studies (n = 417 523) reported harms. Statins were significantly associated with decreased risk of all-cause mortality (risk ratio [RR], 0.92 [95% CI, 0.87 to 0.98]; absolute risk difference [ARD], −0.35% [95% CI, −0.57% to −0.14%]), stroke (RR, 0.78 [95% CI, 0.68 to 0.90]; ARD, −0.39% [95% CI, −0.54% to −0.25%]), myocardial infarction (RR, 0.67 [95% CI, 0.60 to 0.75]; ARD, −0.85% [95% CI, −1.22% to −0.47%]), and composite cardiovascular outcomes (RR, 0.72 [95% CI, 0.64 to 0.81]; ARD, −1.28% [95% CI, −1.61% to −0.95%]); the association with cardiovascular mortality was not statistically significant (RR, 0.91 [95% CI, 0.81 to 1.02]; ARD, −0.13%). Relative benefits were consistent in groups defined by demographic and clinical characteristics, although data for persons older than 75 years were sparse. Statin therapy was not significantly associated with increased risk of serious adverse events (RR, 0.97 [95% CI, 0.93 to 1.01]), myalgias (RR, 0.98 [95% CI, 0.86 to 1.11]), or elevated alanine aminotransferase level (RR, 0.94 [95% CI, 0.78 to 1.13]). Statin therapy was not significantly associated with increased diabetes risk overall (RR, 1.04 [95% CI, 0.92 to 1.19]), although 1 trial found high-intensity statin therapy was significantly associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). Otherwise, there were no clear differences in outcomes based on statin intensity. <h3>Conclusions and Relevance</h3> In adults at increased CVD risk but without prior CVD events, statin therapy for primary prevention of CVD was associated with reduced risk of all-cause mortality and CVD events. Benefits of statin therapy appear to be present across diverse demographic and clinical populations, with consistent relative benefits in groups defined by demographic and clinical characteristics.